Effects of short-term strenuous endurance exercise upon corpus luteum function.

PURPOSE: The present study tested whether short-term, abruptly initiated training can cause corpus luteum dysfunction when exercise is limited to either the follicular or luteal phase of the cycle. METHODS: Reproductive hormone excretion and menstrual characteristics were studied in sedentary women who exercised only during the follicular (N = 5) or the luteal (N = 4) phase. Six women served as controls, three of whom exercised at a low volume and three who remained sedentary. Weekly progressive increments in exercise volume continued until either ovulation (follicular group) or menses (luteal group) occurred. Physical activity and nutrient intake were closely monitored with the intent to maintain body weight. RESULTS: No luteal phase disturbances occurred in any of the control subjects, whereas 40% of follicular and 50% of luteal exercisers experienced luteal defects. The proportion of menstrual cycles disrupted was not different between luteal and follicular exercisers (50% vs 30%, respectively) but was significantly greater than the proportion of cycles disrupted in control subjects (P < 0.05). CONCLUSIONS: These results suggest that exposure to abrupt onset of training can alter luteal function, regardless of the menstrual cycle phase in which exercise occurs. This study also demonstrates that a relatively low volume of exercise suffices to induce mild disturbances in luteal function.

Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women.

OBJECTIVE: Current studies reveal little regarding the inception of exercise-induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic-pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. SUBJECTS: All subjects were eumenorrhoeic, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (VO2max = 38.0 +/- 1.8) (mean +/- SEM) ml/kg/min). DESIGN: All women completed a 13.5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake (n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4.5 hours before and 8 hours after one hour of exercise and or strolling. MEASUREMENTS: A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. RESULTS: Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0.05). Strolling produced no significant changes in LH secretion. CONCLUSION: Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse.

Nalmefene enhances LH secretion in a proportion of oligo-amenorrheic athletes.

The influence upon LH secretion of doses of nalmefene, an orally effective congener of naloxone, and a placebo was compared in nine oligo-amenorrheic athletes with that in five regularly menstruating non-athletic women as a test for periodic elevations in hypothalamic opioid tone. After a 360-min control period, LH levels were followed for an additional 360 min following ingestion of the medications in random order approximately six weeks apart, 10-min blood sampling being employed throughout. The mean amplitude post-nalmefene in the athletes was significantly greater than pre (p < 0.05), although there were no differences in the frequency of LH pulses after placebo or nalmefene ingestion. Subjects were labelled as "responders" if their peak AUC after treatment exceeded their pretreatment AUC for LH by more than 1.96 SD (p < 0.05). There were no placebo responders, but 5/9 of the athletes and 1/5 of the menstruating controls were classified as nalmefene responders (p < 0.05). In addition, a variable proportion of the athletes (but none of the controls) experienced symptoms suggestive of narcotic withdrawal 1-4 h after ingesting nalmefene and again 12-18 h later. It appears that demonstrable increases in opioid tone occur at least transiently in a proportion of oligo-amenorrheic athletes.

Exercise induces two types of human luteal dysfunction: confirmation by urinary free progesterone.

We have previously reported that during 2 months of strenuous exercise, untrained young women with documented ovulatory menstrual cycles developed secondary oligoamenorrhea and luteal phase defects. In this study we tested the hypothesis that such abnormalities arise by altered neuroendocrine regulation of menstrual hormone secretion and that weight loss potentiates such effects. We supply a detailed analysis of the 20 cycles, of the total of 53, in which luteal phase abnormalities occurred. During the control month and 2 exercise months, all subjects collected daily overnight urine samples for the determination of LH, FSH, estriol (E3), and free progesterone (P) excretion by RIAs and creatinine by chemical assay. The characteristics of the abnormal luteal phase cycles were determined by comparing the excreted hormone levels and patterns during the control cycles with those of exercise cycles. The area under the curve (AUC) for each hormone was calculated for the follicular and luteal phases of each cycle. Six of the exercise cycles exhibited an inadequate luteal phase. This was characterized by a mean integrated P area of 202.4 (SEM, -61.8) nmol/day.nmol creatinine, compared with 331.7 (SEM, 64.7) during the corresponding control cycles, over a period of 9 or more days after the urinary LH peak to the onset of menses. Fourteen of the exercise cycles exhibited a short luteal phase. This was characterized by a mean integrated P area of 75.9 (30.9) nmol/day.nmol creatinine, compared to 267 (61.7) during the corresponding control cycles, over a span of 8 days or less from the urinary LH peak to the onset of menses. Additional abnormalities occurred only in the short luteal phase cycles. These included an increase in the length and AUC for E3 of the follicular phase and a decrease in the AUC of LH during the luteal phase. We conclude that the initiation of strenuous endurance training in previously ovulating untrained women frequently leads to corpus luteum dysfunction associated with insufficient P secretion and, in the case of short luteal phase cycles, decreased luteal phase length. That exercise may alter the neuroendocrine system is suggested by a delay in the ovulatory LH peak in spite of increased E3 excretion; moreover, less LH is excreted during the luteal phase. The lack of positive feedback to estrogens and decreased LH secretion during the luteal phase could compromise corpus luteum function. In contrast, decreased free P excretion was the sole abnormality noted in menstrual cycles with an inadequate luteal phase.

Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids.

PURPOSE: The effects of hydroxychloroquine (HCQ) on serum levels of cholesterol, triglycerides, and high- (HDL) and low-density lipoprotein (LDL) were studied in patients with rheumatoid arthritis or systemic lupus erythematosus. PATIENTS AND METHODS: A total of 155 women were divided into the following treatment groups: Group A: patients taking HCQ and no steroids (n = 58); Group B: patients taking steroids and no HCQ (n = 35); Group C: patients receiving both HCQ and steroids (n = 18); and Group D: patients receiving neither HCQ nor steroids (n = 44). RESULTS: HCQ therapy had a high statistical association with low serum levels of cholesterol (181 mg/dL; p = 0.0006), triglycerides (106 mg/dL; p = 0.0459), and LDL (101 mg/dL; p = 0.0004), irrespective of concomitant steroid administration. The HCQ-treated group (A) had lower cholesterol (181 mg/dL; p = 0.0039) and LDL (101 mg/dL; p = 0.007) levels than those receiving neither HCQ nor steroids (205 mg/dL) and 128 mg/dL) (Group D). No HDL differences were observed. CONCLUSION: The effects of HCQ do not appear to be due to changes in diet or weight, and the drug was well tolerated. Although the mechanism of cholesterol lowering by HCQ is not known, this drug deserves further investigation for its lipid-lowering properties.

The detection of peaks in luteinizing hormone secretion.

Fluctations in luteinizing hormone are believed to consist of irregularly spaced sharp increases separated by periods of exponential decay. A simple method is presented for analysing such fluctuations when the data consist of uniformly sampled observations of hormone. Specific allowance for the exponential decay in the absence of pulses is made via a time series model before assessing the number and extent of pulses. All calculations are done using MINITAB regression programs. The results have been compared with those obtained by three established models and are in general agreement.

Melatonin response to exercise training in women.

Previous human studies have indicated that daytime melatonin levels increase when the organism is subjected to the stress of fasting and exercise. Melatonin, epinephrine, and norepinephrine levels were measured during a mock run and in the course of treadmill exercise performed before (T-1), during (T-2), and following (T-3) a progressive conditioning (running) program. Hormonal responses to the training program were determined by comparing values at T-1 and T-3. Plasma melatonin, epinephrine, and norepinephrine levels rose significantly (P less than .01) from baseline values for each exercise intensity during all three treadmill runs. While a dose-response trend was observed in each of the norepinephrine and epinephrine trials, there appeared to be a progressive diminution of this relationship in melatonin between intensities. Further, as training progressed, the peak melatonin concentration was decreased by 52% from T-1 to T-3, while peak epinephrine and norepinephrine values diminished only 19% and 8%, respectively. These results suggest that vigorous exercise training may attenuate rather than augment the secretion of pineal melatonin. Development of a human model of pineal responsiveness to exercise may contribute to the elucidation of exercise-associated reproductive disorders.

MSH/ACTH 4-10 and aging effects on delayed response performance in rats.

The present study examines the effect of MSH/ACTH 4-10 on delayed response performance (DRP) in a two choice version of the Hunter paradigm incorporating the Honzik opaque door modification. DRP was measured in male, Long-Evans rats after administration (IP) of various doses of MSH/ACTH 4-10 or control when animals were young (3 months) and aged (30 months) and aged (30 months). Between MSH/ACTH dose response observations animals received a variety of psychoactive agents of various classes prior to DRP assessment. In addition, DRP was assessed once per month, without drug, from ages 10 to 30 months. MSH/ACTH 4-10, at a dose of 95 ug/kg, significantly enhanced retention of a visual stimulus, while larger doses of MSH/ACTH 4-10 impaired delayed response performance in animals when young. Reversal of anticholinergic-induced DRP impairments by physostigmine and MSH/ACTH 4-10, but not strychnine or methylphenidate, suggests that the effect of MSH/ACTH 4-10 on DRP is specific and may be mediated by enhancement of the cholinergic system(s) in the CNS. Animals began to demonstrate significant impairment in DRP, at longer delays, at the age of 23 months. While confounds such as changes in sensory acuity, motor performance and food preference cannot be totally ignored, the assessment of performance at shorter delay periods served as a control for these problems. No significant age-related changes in DRP at shorter periods of delay were found, indicating that perception and motor capabilities played little role in age-related DRP alterations. Trend analysis revealed that animals demonstrate significant linear and quadratic MSH/ACTH 4-10 dose responses which appear as an inverted "U" in the Hunter paradigm when young. As animals age, this dose response becomes a purely positive linear relationship. Thus, the age-induced decrease in acetylcholine (ACh) levels, and hence MSH/ACTH peptide-induced release, may result in the change in MSH/ACTH dose response profiles. These findings may have clinical implications in the treatment of age-induced or Alzheimer's related cognitive pathologies, which are of cholinergic etiology.

The effect of MSH/ACTH 4-10 on delayed response performance and post-test locomotor activity in rats.

Delayed response performance was measured in male, Long-Evans rats 1 hr after IP administration of various doses of MSH/ACTH 4-10 or control in a Hunter delayed reaction apparatus. Additional treatments consisting of naloxone 500 micrograms/kg (IP) and naloxone 500 micrograms/kg in conjunction with MSH/ACTH 4-10 95 micrograms/kg were also administered. Directly after delayed response performance was assessed, gross locomotor activity was determined. MSH/ACTH 4-10, at a dose of 95 micrograms/kg, significantly enhanced retention of a visual stimulus, while MSH/ACTH 4-10, at doses of 195 and 285 micrograms/kg, significantly impaired delayed response performance. Naloxone treatment resulted in significantly impaired delayed response performance when compared to control. However, naloxone plus MSH/ACTH 4-10 treatment failed to produce a significant difference from control in the delayed response performance paradigm. In post-test locomotor activity determination, an apparent dose-response existed for MSH/ACTH 4-10 with the two highest doses (190 and 285 micrograms/kg) resulting in significantly increased locomotor activity. The observed delayed response performance data support theories implicating MSH/ACTH peptides in attentional processes involving visual stimuli. The fact that large doses of MSH/ACTH 4-10 disrupt delayed response performance while increasing post-test activity suggest that an optimum level of effect caused by the MSH/ACTH peptide exists in this paradigm.

Sleep-wave activity of a delta sleep-inducing peptide analog correlates with its penetrance of the blood-brain barrier.

Delta sleep-inducing peptide (DSIP) significantly increases delta wave electrical activity in the brain of rats after intraperitoneal (i.p.) injection. Rats (n = 10) were peripherally injected with DSIP and [D-Ala4]DSIP-NH2 during the dark portion of a 12-h light/dark cycle prior to recording of epidural encephalographic (EEG) wave forms. Administration of [D-Ala4]DSIP-NH2, an analog that enters the brain after peripheral administration more readily than the parent DSIP molecule, resulted in significantly more delta waves than DSIP together with a highly significant amount of theta activity. DSIP was found to significantly increase EEG output in the delta range when compared with controls. In addition, the DSIP analog significantly decreased locomotor activity, whereas DSIP itself was without effect. These findings strongly support the controversial concepts that peripherally injected peptides can reach the brain and that DSIP compounds can increase sleep activity.

Induction of menstrual disorders by strenuous exercise in untrained women.

We performed a prospective study of 28 initially untrained college women with documented ovulation and luteal adequacy to determine whether strenuous exercise spanning two menstrual cycles would induce menstrual disorders. To ascertain the influence, if any, that weight loss might exert, we randomly assigned the subjects to weight-loss and weight-maintenance groups. Subjects were expected to run 4 miles (6.4 km) per day, progressing to 10 miles (16.1 km) per day by the fifth week, and to engage daily in 31/2 hours of moderate-intensity sports. The normalcy of the menstrual cycles during the period of exercise was judged independently according to clinical and hormonal criteria, the latter comprising serial measurements of gonadotropin and sex-steroid excretion. A higher percentage of abnormalities proved to be detectable by hormonal means (P less than 0.02). Only four subjects (three in the weight-maintenance group) had a normal menstrual cycle during training. In the weight-loss group, the number of women who had luteal abnormalities as compared with those who lost the surge in luteinizing hormone altered significantly over time, the latter occurring more frequently (P less than 0.01) as training progressed. Within six months of termination of the study, all subjects were again experiencing normal menstrual cycles. We conclude that vigorous exercise, particularly if compounded by weight loss, can reversibly disturb reproductive function in women.

Effect of high doses of naloxone on shuttle avoidance acquisition in rats.

Administration of high doses of naloxone intraperitoneally (2.5-10.0 mg/kg) resulted in a dose-related impairment of avoidance response acquisition in a shuttle avoidance paradigm in rats. Naloxone in this dose range produced a significant decrease in the number of intertrial responses but did not result in a significant dose-response. Escape latencies were not affected by naloxone administration at any dose tested. The effect of naloxone on activity and nociception are implicated as possible causes of the observed behavior. The results are discussed as behavioral evidence supporting theories postulating multiple opiate receptors.